Retraction Note: Antisense oligonucleotides targeting midkine induced apoptosis and increased chemosensitivity in hepatocellular carcinoma cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Retraction Note: Antisense oligonucleotides targeting midkine inhibit tumor growth in an in situ human hepatocellular carcinoma model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An outbreak of epidemic keratoconjunctivitis caused by human adenovirus type 8 in primary school, southwest China.

BACKGROUND: Two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively with an interval of 5 days in two primary boarding schools in Weixi Lisu Autonomous County, Diqing, and Tibetan Autonomous Prefecture, Yunnan. The aims of this study were to determine the intensity and characteristics of the outbreaks, as well as the clinical manifestations in the patients, the risk factors for infection and the pathogen responsible for the two outbreaks. METHODS: An outbreak investigation was conducted in two primary schools, and a case-control study including patients from the Weixi County Ethnic Primary School was performed. Relevant specimens were collected according to the case definition, and next-generation sequencing was employed to identify the pathogen. An epidemiological investigation method was used to analyse the related epidemiological characteristics, such as risk factors. The phylogenetic tree was constructed by MEGA 7.0. RESULTS: A total of 331 acute conjunctivitis cases, including probable cases of EKC, were reported in the two schools, and the attack rates were 30.59% (171/559, 95%CI: 26.76-34.42) and 20.41% (160/784, 95%CI: 17.58-23.24), respectively. Cases occurred in all grades and classes in both schools, and only one staff member in each school presented illness. The epidemics lasted for 54 days and 45 days, respectively. The patients had typical manifestations of EKC, such as acute onset, follicular hyperplasia, pseudomembrane formation, preauricular lymphadenopathy, corneal involvement and blurred vision, and a relatively long disease course (average 9.40 days, longest 23 days and shortest 7 days). The risk factor for infection was close contact with a patient or personal items contaminated by a patient. The pathogen responsible for the outbreaks was HAdV-8. The virus was highly similar to the 2016 HAdV-8 strain from Tibet, China. CONCLUSIONS: This study strongly suggests that HAdV-8 could lead to serious consequences. This is the second report of a HAdV-8-associated EKC outbreak in mainland China. Tibetan HAdV-8 might be circulating in southwest China; therefore, it is necessary to monitor the pathogens causing acute conjunctivitis in this area.

[Analysis of sites of Toxoplasma gondii SAG2 gene in blood of HIV-positive people in Lincang City, Yunnan Province].

OBJECTIVE: To preliminarily understand the genotype characteristics of Toxoplasma gondii in blood of HIV-positive persons in Lincang City, Yunnan Province. METHOD: Two segments of SAG2 gene of T. gondii from blood samples of HIV-positive persons in Lincang City were extracted and amplified by using the nested PCR method and the genotype was identified and compared with the standard strain (Type I) of Toxoplasma gondii. RESULTS: Thirty-five SAG2 genes (241 bp) and 35 SAG2 genes (221 bp) of T. gondii were amplified from 170 blood samples of the HIV-positive people, and 4 of each case were selected and digested with enzyme, then 2 aim gene fragments of each case were chosen and compared with the standard strain (Type I) of T. gondii. The digestion of SAG2 gene (241 bp) showed the genotype of the blood samples was Type I or Type II, and the digestion of SAG2 gene (221 bp) confirmed that the genotype was Type I. CONCLUSION: It is preliminarily confirmed that the genotype of T. gondii in blood of HIV-positive persons in Lincang City, Yunnan Province is Type I.

Enhanced therapeutic effects of combined chemotherapeutic drugs and midkine antisense oligonucleotides for hepatocellular carcinoma.

AIM: To evaluate the effect of combined antisense oligonucleotides targeting midkine (MK-AS) and chemotherapeutic drugs [cisplatin(DDP), 5-fluorouracil (5-FU) and adriamycin (ADM)] on inhibition of HepG2 cell proliferation, and to analyze the efficacy of MK-AS used in combined ADM in in situ human hepatocellular carcinoma (HCC) model. METHODS: HepG2 cells were treated with MK-AS and/or chemotherapeutic drugs mediated by Lipofectin, and cell growth activity was determined by MTS assay. An in situ HCC model was used in this experiment. MK-AS, ADM and MK-AS + ADM were given intravenously for 20 d, respectively. The animal body weight and their tumor weight were measured to assess the effect of the combined therapy in vivo. RESULTS: Combined treatment with MK-AS reduced the IC50 of DDP, 5-FU and ADM in HepG2 cells. MK-AS significantly increased the inhibition rate of DDP, 5-FU and ADM. Additionally, synergism (Q 1.15) occurred at a lower concentration of ADM, 5-FU and DDP with combined MK-AS. Combined treatment with MK-AS and ADM resulted in the more growth inhibition on in situ human HCC model compared with treatment with chemotherapeutic drugs alone. CONCLUSION: MK-AS increases the chemosensitivity in HepG2 cells and in situ human HCC model, and the combination of MK-AS and ADM has a much better in vitro and in vivo synergism.

Antisense oligonucleotide targeting midkine suppresses in vivo angiogenesis.

AIM: To evaluate the effect of antisense oligonucleotide targeting midkine (MK-AS) on angiogenesis in chick chorioallantoic membrane (CAM) and in situ human hepatocellular carcinoma (HCC). METHODS: An in situ human hepatocellular carcinoma (HCC) model and CAM assay were used in this experiment. The effect of MK-AS on angiogenesis was evaluated by cell proliferation assay and hematoxylin-eosin (HE) staining. RESULTS: MK-AS significantly inhibited human umbilical vein endothelial cells (HUVEC) and in situ human HCC growth. At the same time, MK-AS suppressed the angiogenesis both in human hepatocellular carcinoma cell line (HEPG2)-induced CAM and in situ human HCC tissues. CONCLUSION: MK-AS is an effective antiangiogenesis agent in vivo.

Antisense oligonucleotides targeting midkine inhibit tumor growth in an in situ human hepatocellular carcinoma model.

AIM: To evaluate the in vivo antitumor effects of antisense oligonucleotides targeting midkine (MK-AS). METHODS: An in situ human hepatocellular carcinoma (HCC) model was established in mice livers orthotopically. The MK-AS and 5- fluorouracil (5-Fu) were administered intravenously. The tumor sizes and plasma alpha-fetoprotein (AFP) were measured by calipers and radiation immunoassay respectively. The morphology of tumors was evaluated by hematoxylin-eosin staining of histological sections. Human MK, p53, Bax, Bcl-2, and caspase-3 protein content were detected by Western blotting. RESULTS: MK-AS significantly inhibited in situ human HCC growth in mice compared with the saline group in a dose-dependent manner. After the treatment with MK-AS or with 5-Fu, the plasma AFP concentration decreased in a dose-dependent manner. Interestingly, MK-AS also clearly downregulated the protein level of Bcl-2, and upregulated p53, Bax, and caspase-3 in the hepatocellular carcinoma tissue. CONCLUSION: These results demonstrated that MK-AS was an effective antitumor antisense oligonucleotide in vivo in mice; its antitumor effect is associated with the increase of pro-apoptotic proteins, such as p53, Bax, and caspase-3, and the decrease of the anti-apoptotic protein, Bcl-2.

Antisense oligonucleotides targeting midkine induced apoptosis and increased chemosensitivity in hepatocellular carcinoma cells.

AIM: Overexpression of midkine (MK) has been observed in many malignancies. This aim of this study is to screen for suitable antisense oligonucleotides (ASODN) targeting MK in hepatocellular carcinoma (HCC) cells and evaluate its antitumor activity. METHODS: Ten ASODN targeting MK were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. In addition, MK mRNA, protein levels, as well as apoptosis and caspase-3 activity were also examined in HepG2 cells. Cell proliferation was then analyzed after treatment with both ASODN and chemotherapeutic drugs. RESULTS: In this experiment, the ASODN5 among the 10 ASODN showed higher inhibitory activity against proliferation of hepatocellular carcinoma cells in a dose-dependent manner. In HepG2 cells, ASODN5 could significantly reduce the MK mRNA level and protein content. After transfection with ASODN5 for 48 h, accompanied with a decline of survivin and Bcl-2 protein content, a remarkable increase of apoptosis and caspase-3 activity was observed in HepG2 cells. Furthermore, ASODN5 transfer can significantly increase chemosensitivity in HepG2 cells. CONCLUSION: Antisense oligonucleotides targeting MK shows therapeutic effects on HCC; ASODN5 has the possibility to be developed as an effective antitumor agent.

Antisense oligonucleotide targeting p53 increased apoptosis of MCF-7 cells induced by ionizing radiation.

AIM: To investigate the effect of antisense compounds (AS) targeting human p53 mRNA on radiosensitivity of MCF-7 cells. METHODS: Western blotting and RTPCR were used to analyze the protein content and mRNA level. Additionally, cell proliferation, cell cycle and cell apoptosis were all analyzed in irradiated or sham-irradiated cells. RESULTS: Among the five antisense compounds (AS), AS3 was identified to efficiently inhibit p53 mRNA level and protein content. Interestingly, AS3 transfer has little effect on cell proliferation in DU-145 cells (mutant p53) after ionizing radiation (IR). In contrast, a marked increase of cell apoptosis and growth inhibition were observed in MCF-7 cells (wild-type p53), suggesting that AS3 can increase radiosensitivity of MCF-7 cells. Additionally, it was also observed that the transfection of AS3 decreased the fraction of G1 phase cells, and increased the proportion of S phase cells compared to untreated cells 24 h after IR in MCF-7 cell lines. CONCLUSION: AS3 transfection increases MCF-7 cell apoptosis induced by 5 Gy-radiation, and this mechanism may be closely associated with abrogation of G1 phase arrest.

[Significance of detection of serum sialic acid and Epstein-Barr virus VCA-IgA in diagnosis and monitoring radiotherapy effectiveness in nasopharyngeal carcinoma patients].

BACKGROUND: To understand the significance of detection of serum sialic acid (SA) and Epstein-Barr virus VCA-IgA (EBV-CA-IgA) in diagnosis and monitoring radiotherapy effectiveness of nasopharyngeal carcinoma (NPC) patients. METHODS: Serum SA and EBV-CA-IgA were detected in 65 cases with NPC before radiotherapy and one months after radiotherapy and 21 cases one year after radiotherapy for NPC with local recurrence and/or distant metastasis. Healthy persons and patients with benign lesions of head and neck were also enrolled as control group. RESULTS: SA and EBV-CA-IgA of NPC patients before radiotherapy were significantly higher than those in control group (P<0.01). The sensitivity of combination of SA and EBV-CA-IgA (96.9%) was higher than those determined alone (P<0.05). The SA level of NPC patients after radiotherapy and without recurrence after radiotherapy was reduced significantly compared to the NPC patients before radiotherapy (P<0.01). The SA level of NPC patients with recurrence was significantly higher than that in NPC patients without recurrence (P<0.01), whereas the positive rate of EBV-CA-IgA changed little. CONCLUSION: Dynamic detection of serum SA may be a valuable technique for diagnosis and monitoring radiotherapy effectiveness in NPC patients. The combined determination of the two indexes can raise the positive rate of patients with NPC.

Effect of early administration of exogenous basic fibroblast growth factor on acute edematous pancreatitis in rats.

AIM: To observe the therapeutic effect of early administration of exogenous Basic fibroblast growth factor (bFGF) on acute edematous pancreatitis (AEP) in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three (n = 10): normal control group (group I), AEP group (group II) and AEP with bFGF treatment group (group III). AEP was induced by subcutaneous injection of cerulein (5.5 microg/kg and 7.5 microg/kg) at 1 h interval into rats of groups II and III. Three hours after induction of AEP, 100 microg/kg bFGF was administrated intraperitoneally for 1 h to group III rats. For test of DNA synthesis in acinar cells, 5-bromo-2'-deoxyuridine (BrdU) labeling solution was intraperitoneally injected into the rats of groups II and III 24 h after bFGF treatment. The changes in serum amylase, lipase, pancreatic tissue wet/dry ratio were detected. RESULTS: In bFGF treatment group, there was a significant decrease in the volume of serum amylase, lipase and the pancreatic wet/dry weight ratio(1383.0+/-94.6 U/L, 194.0+/-43.6 U/L, 4.32+/-0.32) compared to AEP group (3464+/-223.7 U/L, 456+/-68.7 U/L, 6.89+/-0.47) (P < 0.01), and no significant difference was found between bFGF treatment and control group (1289+/-94.0 U/L, 171+/-23.4 U/L, 4.12+/-0.26, P > 0.05). The inflammatory changes such as interstitial edema, polymorphonuclear neutrophils (PMNs) and vacuolization were significantly ameliorated compared to AEP group (P < 0.01). A small number of BrdU-labeled nuclei were observed in acinar cells of AEP rats (1.8+/-0.3 nuclei/microscopic field, n = 10) while diffuse BrdU-labeled nuclei were found in bFGF-treated rats (18.9+/-1.4 nuclei/microscopic field, n = 10) (P < 0.01). Immunohistochemical study showed increased DNA synthesis in pancreatic acinar cells. CONCLUSION: Early administration of exogenous bFGF has significant therapeutic effect on cerulein-induced acute edematous pancreatitis in rats. Its mechanism is related to the amelioration of inflammation and facilitation of pancreatic regeneration.

[Effect of oxymatrine on serum matrix metalloproteinase-2 and its inhibitor in patients with chronic hepatitis B and liver cirrhosis].

OBJECTIVE: To observe the effect of oxymatrine on the level of serum matrix metalloproteinase-2 (MMP-2) and its inhibitor (TIMP-2) in patients with chronic hepatitis B (CHB) and post-hepatitis B liver cirrhosis (LC), as well as on liver fibrosis indexes as hyaluronic acid (HA), laminin (LN) and IV type collagen (IV C). METHODS: Changes of all the above-mentioned indexes in patients with CHB (n = 36) and LC (n = 36) before and after treatment were determined, and the relationship of MMP-2 and TIMP-2 with liver fibrosis indexes were analyzed. RESULTS: Oxymatrine could decrease the levels of MMP-2, HA, LN and IV C in patients with severe or moderate CHB and LC of Child-pugh A, B and C grade, as compared with the data before treatment (P < 0.05). Serum level of MMP-2 and TIMP-2 was well correlated with the levels of liver cirrhosis indexes. CONCLUSION: MMP-2 and TIMP-2 can be used as a reference for evaluating the degree of LC, and oxymatrine has a certain anti-LC effect.